Growth Factors (GFs), such as Epidermal Growth Factor (EGF) and insulin- like Growth Factors (IGFs)-I and -II are present in most mammalian milks in concentrations sufficient to have biological effects. The preceding Project #1 (PI: O. Koldovsky) dealt with the sources of the mentioned GFs for the neonate. The purpose of this project is to examine the hypothesis that milk-borne GFs influence both growth and differentiation of the gastrointestinal tract (GI) of the suckling, and also have effects at sites distal to the GI tract. Studies dealing specifically with the effect on the liver and its function are the subject of Project #3 (PI: R. McCuskey). To test the hypothesis that milk-borne GFs affect the growth and development of the gastrointestinal (GI) tract and beyond, we will feed suckling rats either RMS or RMS supplemented with EGF, IGF-I and IGF- II individually, and in combination, in doses corresponding to the intake of these GF-s in milk. We hypothesize that feeding of GF-supplemented RMS to suckling rats will produce dose dependent changes in the growth of specific organs, including the liver, brain, cardiac and striated muscle, stomach and small bowel, and that IGFs and/or EGF fed to sucklings will stimulate cellular differentiation both locally (GI tract) and distally (eye, ear, etc.) To test the hypothesis that milk-borne GFs significantly alter a number of specific GI tract functions when given to the suckling chronically, we will study changes in several specific GI functions; namely, gastric evacuation, intestinal propulsive motility, and intestinal transport in suckling rats fed with RMS or RMS supplemented with GFs. Furthermore, we will explore the mechanisms involved in the absorption of GFs by the neonatal GI tract. The specificity of the inhibitable process for GF absorption from the GI tract will be tested by determining effects of excess EGF, TGFa, and IGFs on GF peptide absorption using the jejunal and ileal loop models of in vivo absorption. Since rat milk is known to contain factors that inhibit degradation of several peptide hormones by rat gastric and intestinal juices in vitro, we will characterize further (using HPLC) the fractions of rat milk responsible for this protective property and analyze their role in the mechanism of GI absorption of GF in suckling rats. We will also test the hypothesis that an enterohepatic circulation of IGFs exists, contributing to the increase of effectiveness of milk-borne and endogenously produced IGFs. Lastly, we will test the hypothesis that a milk-borne source of epidermal growth factor and insulin-like growth factors functions in the regulation of whole body long-chain fatty acid oxidation capacity in the suckling rat.